Daxx interacts with and modulates the activity of CREB

Yen Sung Huang, Che Chang Chang, Tien Chi Huang, Yung Lin Hsieh, Hsiu Ming Shih

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The phosphorylation of cAMP response element-binding protein (CREB) induced by the cAMP-dependent protein kinase A (PKA) elicits the recruitment of CREB-binding protein (CBP) for activating cAMP responsive gene expression. Several reports indicate that proteins binding to CREB and/or CBP play important roles in modulating the CREB-dependent transactivation. Here, we show that Daxx interacts with CREB and modulates CREB-mediated transcription. Daxx was identified as a CREB-interacting protein by a yeast two-hybrid screen. Depletion of endogenous Daxx by specific shRNA or overexpression of Daxx resulted in decreased or increased levels of the cAMP/PKA-induced reporter activity and target gene expression, respectively. In vitro and in vivo binding studies revealed that Daxx C-terminal domain binds to CREB basic leucine zipper domain. The binding of Daxx to CREB correlates with its repressive effect on a CRE-mediated reporter activity induced by forskolin or PKA. Furthermore, the results of electrophoresis mobility shift assays and chromatin immunoprecipitation experiments showed that Daxx attenuated the DNA binding potential of the CREB. Our study provides a previously undescribed role of Daxx in repressing cAMP-responsive gene expression and also a mechanism underlying the repressive effect of Daxx on CREB transcriptional potential.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalCell Cycle
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

Fingerprint

Cyclic AMP Response Element-Binding Protein
Cyclic AMP-Dependent Protein Kinases
Gene Expression
Protein Binding
CREB-Binding Protein
Leucine Zippers
Fungal Proteins
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Colforsin
Small Interfering RNA
Transcriptional Activation
Electrophoresis
Carrier Proteins
Phosphorylation

Keywords

  • cAMP-responsive-element-binding protein (CREB)
  • Death-associated protein 6 (Daxx)
  • PKA
  • SUMO-interacting motif
  • Sumoylation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Huang, Y. S., Chang, C. C., Huang, T. C., Hsieh, Y. L., & Shih, H. M. (2012). Daxx interacts with and modulates the activity of CREB. Cell Cycle, 11(1), 99-108. https://doi.org/10.4161/cc.11.1.18430

Daxx interacts with and modulates the activity of CREB. / Huang, Yen Sung; Chang, Che Chang; Huang, Tien Chi; Hsieh, Yung Lin; Shih, Hsiu Ming.

In: Cell Cycle, Vol. 11, No. 1, 01.01.2012, p. 99-108.

Research output: Contribution to journalArticle

Huang, YS, Chang, CC, Huang, TC, Hsieh, YL & Shih, HM 2012, 'Daxx interacts with and modulates the activity of CREB', Cell Cycle, vol. 11, no. 1, pp. 99-108. https://doi.org/10.4161/cc.11.1.18430
Huang, Yen Sung ; Chang, Che Chang ; Huang, Tien Chi ; Hsieh, Yung Lin ; Shih, Hsiu Ming. / Daxx interacts with and modulates the activity of CREB. In: Cell Cycle. 2012 ; Vol. 11, No. 1. pp. 99-108.
@article{80a05dafefdb4c27b76f122a48dc4624,
title = "Daxx interacts with and modulates the activity of CREB",
abstract = "The phosphorylation of cAMP response element-binding protein (CREB) induced by the cAMP-dependent protein kinase A (PKA) elicits the recruitment of CREB-binding protein (CBP) for activating cAMP responsive gene expression. Several reports indicate that proteins binding to CREB and/or CBP play important roles in modulating the CREB-dependent transactivation. Here, we show that Daxx interacts with CREB and modulates CREB-mediated transcription. Daxx was identified as a CREB-interacting protein by a yeast two-hybrid screen. Depletion of endogenous Daxx by specific shRNA or overexpression of Daxx resulted in decreased or increased levels of the cAMP/PKA-induced reporter activity and target gene expression, respectively. In vitro and in vivo binding studies revealed that Daxx C-terminal domain binds to CREB basic leucine zipper domain. The binding of Daxx to CREB correlates with its repressive effect on a CRE-mediated reporter activity induced by forskolin or PKA. Furthermore, the results of electrophoresis mobility shift assays and chromatin immunoprecipitation experiments showed that Daxx attenuated the DNA binding potential of the CREB. Our study provides a previously undescribed role of Daxx in repressing cAMP-responsive gene expression and also a mechanism underlying the repressive effect of Daxx on CREB transcriptional potential.",
keywords = "cAMP-responsive-element-binding protein (CREB), Death-associated protein 6 (Daxx), PKA, SUMO-interacting motif, Sumoylation, Transcriptional regulation",
author = "Huang, {Yen Sung} and Chang, {Che Chang} and Huang, {Tien Chi} and Hsieh, {Yung Lin} and Shih, {Hsiu Ming}",
year = "2012",
month = "1",
day = "1",
doi = "10.4161/cc.11.1.18430",
language = "English",
volume = "11",
pages = "99--108",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "1",

}

TY - JOUR

T1 - Daxx interacts with and modulates the activity of CREB

AU - Huang, Yen Sung

AU - Chang, Che Chang

AU - Huang, Tien Chi

AU - Hsieh, Yung Lin

AU - Shih, Hsiu Ming

PY - 2012/1/1

Y1 - 2012/1/1

N2 - The phosphorylation of cAMP response element-binding protein (CREB) induced by the cAMP-dependent protein kinase A (PKA) elicits the recruitment of CREB-binding protein (CBP) for activating cAMP responsive gene expression. Several reports indicate that proteins binding to CREB and/or CBP play important roles in modulating the CREB-dependent transactivation. Here, we show that Daxx interacts with CREB and modulates CREB-mediated transcription. Daxx was identified as a CREB-interacting protein by a yeast two-hybrid screen. Depletion of endogenous Daxx by specific shRNA or overexpression of Daxx resulted in decreased or increased levels of the cAMP/PKA-induced reporter activity and target gene expression, respectively. In vitro and in vivo binding studies revealed that Daxx C-terminal domain binds to CREB basic leucine zipper domain. The binding of Daxx to CREB correlates with its repressive effect on a CRE-mediated reporter activity induced by forskolin or PKA. Furthermore, the results of electrophoresis mobility shift assays and chromatin immunoprecipitation experiments showed that Daxx attenuated the DNA binding potential of the CREB. Our study provides a previously undescribed role of Daxx in repressing cAMP-responsive gene expression and also a mechanism underlying the repressive effect of Daxx on CREB transcriptional potential.

AB - The phosphorylation of cAMP response element-binding protein (CREB) induced by the cAMP-dependent protein kinase A (PKA) elicits the recruitment of CREB-binding protein (CBP) for activating cAMP responsive gene expression. Several reports indicate that proteins binding to CREB and/or CBP play important roles in modulating the CREB-dependent transactivation. Here, we show that Daxx interacts with CREB and modulates CREB-mediated transcription. Daxx was identified as a CREB-interacting protein by a yeast two-hybrid screen. Depletion of endogenous Daxx by specific shRNA or overexpression of Daxx resulted in decreased or increased levels of the cAMP/PKA-induced reporter activity and target gene expression, respectively. In vitro and in vivo binding studies revealed that Daxx C-terminal domain binds to CREB basic leucine zipper domain. The binding of Daxx to CREB correlates with its repressive effect on a CRE-mediated reporter activity induced by forskolin or PKA. Furthermore, the results of electrophoresis mobility shift assays and chromatin immunoprecipitation experiments showed that Daxx attenuated the DNA binding potential of the CREB. Our study provides a previously undescribed role of Daxx in repressing cAMP-responsive gene expression and also a mechanism underlying the repressive effect of Daxx on CREB transcriptional potential.

KW - cAMP-responsive-element-binding protein (CREB)

KW - Death-associated protein 6 (Daxx)

KW - PKA

KW - SUMO-interacting motif

KW - Sumoylation

KW - Transcriptional regulation

UR - http://www.scopus.com/inward/record.url?scp=84862949855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862949855&partnerID=8YFLogxK

U2 - 10.4161/cc.11.1.18430

DO - 10.4161/cc.11.1.18430

M3 - Article

C2 - 22185778

AN - SCOPUS:84862949855

VL - 11

SP - 99

EP - 108

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 1

ER -